Quick questions on Apoptosis, disruption to the cell cycle and cancer: VCE Biology Unit 1

Apoptosis is programmed cell death: a regulated, energy-requiring process by which the cell dismantles itself in a controlled way. It is essential for development, tissue homeostasis and elimination of damaged or infected cells.

The central executioners of apoptosis are caspases: cysteine proteases that cleave target proteins. They exist normally as inactive pro-caspases and must be activated by cleavage.

Extrinsic (death receptor) pathway. Triggered by external signals binding to death receptors on the plasma membrane (such as Fas binding FasL on a cytotoxic T cell). The death-receptor complex activates caspase-8 (initiator), which activates caspase-3 (effector).

A cell undergoing apoptosis shows distinctive changes:

Cancer is the disease of unregulated cell division and resistance to apoptosis. It arises when two classes of genes mutate.

Cancer typically requires multiple mutations over time (the multi-hit hypothesis):

Triggered by external signals binding to death receptors on the plasma membrane (such as Fas binding FasL on a cytotoxic T cell). The death-receptor complex activates caspase-8 (initiator), which activates caspase-3 (effector).

Triggered by internal damage signals (such as severe DNA damage detected by p53, or oxidative stress). The mitochondrial outer membrane becomes permeable, releasing cytochrome c into the cytoplasm. Cytochrome c binds Apaf-1 to form the apoptosome, which activates caspase-9 (initiator), which activates caspase-3 (effector).

Normal genes whose products promote cell division (growth factors, growth-factor receptors, signal-transduction proteins, cyclins). A gain-of-function mutation turns a proto-oncogene into an oncogene, producing a hyperactive or constantly-on version that pushes the cell to divide even without a normal signal. Examples: Ras (a signalling switch stuck "on"); HER2 (a growth-factor receptor over-expressed in some breast cancers).

Normal genes whose products inhibit cell division or trigger apoptosis when damage is detected. They act as brakes. A loss-of-function mutation removes the brake.

Apoptosis is regulated, energy-using, controlled and non-inflammatory; necrosis is uncontrolled, passive, and inflammatory.

Caspases are proteases; they cleave specific target proteins. The cleavage cascade dismantles the cell from inside.

A single mutation rarely causes cancer; multiple mutations across both proto-oncogenes and tumour suppressors over time are required.

Proto-oncogenes are the normal versions (good). Oncogenes are the mutated, over-active versions (bad).

Apoptosis is usually a healthy housekeeping process. The problem in cancer is the loss of apoptosis, not its presence.